Functional IL10 and IL12B polymorphisms are associated with persistent Candidaspp. bloodstream infection

Abstract number: O409

Johnson M.D., Plantinga T.S., Scott W.K., van de Vosse E., Velez Edwards D.R., Smith P.B., Alexander B.D., Yang J.C., Laird G., Oosting M., van der Meer J., van Dissel J.T., Kullberg B.J., Netea M.G., Perfect J.R.

Objectives:Candida bloodstream infections cause significant morbidity and mortality in hospitalized patients. While clinical and microbiologic factors affecting prognosis have been identified, the impact of immune responses, mediated by cytokines, on outcomes of infection remains to be studied. The present study assessed the role of genetic variation in cytokine genes on susceptibility and/or clinical outcomes of candidaemia.

Methods: Single nucleotide polymorphisms (SNPs) in six cytokine genes (IFN-g, IL-10, IL-12B, IL-18, IL-1B, IL-8) and one cytokine receptor gene (IL-12RB) were genotyped and analyzed with logistic regression in 365 patients with candidaemia and 351 non-infected controls. In addition, the presence of these SNPs and measured concentrations of pro-inflammatory cytokines were further analyzed for association with persistent fungemia (5 days of positive blood cultures) in 325 Americans with candidaemia. Other variables were assessed including type of Candida spp. identified, total parenteral nutrition (TPN), dialysis dependence, malignancy, immunocompromised state, renal/liver failure. Variables with p < 0.10 on univariate analysis were further analyzed using multivariable logistic regression.

Results: None of the SNPs examined were associated with susceptibility to candidaemia. Mean age of candidaemia patients was 55 years (±21.3), with 44% female, 32% African American, 58% immunocompromised, 31% active malignancy, 10% neutropenic, 43% recent surgery, 21% receiving total parenteral nutrition (TPN), 12% dialysis, 25% liver disease, and 49% ICU residence. The following species were identified: C. albicans (43%), C. glabrata (27%), C. parapsilosis (17%), C. tropicalis (12%), C. krusei (3%), >1 Candida species (6%). Overall, persistent fungemia occurred in 15% of cases. In the multivariable model, persistent candidaemia was significantly associated with (OR, [95% CI]): TPN (2.69 [1.28–5.62]), dialysis dependence (3.45 [1.36–8.74]), IL10 rs1800896 (3.07 [1.31–7.12]) and IL12B rs41292470 (4.34 [1.38–13.8]). In addition, significantly lower pro-inflammatory cytokine concentrations were measured in serum from patients with persistent fungemia.

Conclusions: SNPs in IL-10 and IL12B were associated with persistent fungemia in candidaemia patients, which also associated with low serum concentrations of pro-inflammatory cytokines. This may provide insights for future targeted management strategies for patients with this high mortality condition.